TF12 antibody targets EGP-1 expressed in epithelial cancer: Immunomedics

Jun 14 2010

Immunomedics, Inc. (Nasdaq:IMMU), a biopharmaceutical company focused on developing monoclonal antibodies to treat cancer and other serious diseases, today announced that TF12, in combination with radiolabeled peptides, produced specific, fast, high-contrast imaging and pretargeted radioimmunotherapy of epithelial cancers that include cancers of the prostate and the ovary.

Pretargeting is a novel method developed by IBC Pharmaceuticals, Inc., the Company's majority-owned subsidiary, for delivering radiation or drugs to tissues of interest in 2 steps. The first step involves the administration of a bispecific antibody that targets the tissue of interest. Unlike conventional antibodies which attach to one receptor, bispecific antibodies have been engineered to contain an additional binding site. The presence of a second binding site in a bispecific antibody allows the delivery of radioisotope or drug to take place later in the second step using a small peptide recognizable by the antibody. The advantage of pretargeting is to improve the signal at the tumor relative to the background, or selectively increase the amount of the therapeutic in the tumor.

TF12 is a bispecific antibody constructed using the Company's patented Dock-and-Lock (DNL) protein engineering platform technology. It specifically targets the epithelial glycoprotein-1 antigen (EGP-1 or TROP-2) expressed in many epithelial cancers and has been reported to internalize when bound.

In a mouse model of human prostate cancer, biodistribution studies showed that TF12 in combination with an indium-111-labeled peptide produced excellent tumor-to-blood ratios as early as 2 hours after injection of the radiolabeled peptide.  In addition, the tumors were clearly visualized in a PET scan within 1 hour of the peptide injection with minimal activity in the kidneys.  More importantly, pretargeted therapy with TF12 enhanced median survival to 89 days compared with 67 days from the control groups. 

Separately, in a presentation given earlier at the same annual meeting, preclinical results from studies using TF12 for the pretargeting of ovarian cancer were reported. TF12 labeled with iodine-125 had maximum tumor uptake at 2-6 hours. By 24 hours, when blood concentration was sufficiently reduced for pretargeting, tumor uptake remained 3-fold higher.  Under pretargeting conditions, biodistribution studies in mice showed that tumor localization occurred at 3 hours, which was retained at 24 hours after peptide injection.  At 3 hours, tumor/nontumor ratios were 112 +/- 30, 56 +/- 21, 708 +/- 340 for liver, spleen and blood, respectively.

"In light of the fact that EGP-1 internalizes when bound by an antibody, we are pleased that high tumor uptake and retention of radioactivity was observed in the two cancer models using TF12.  This pretargeting system has the potential for use in the imaging and therapy of epithelial cancers with radionuclides and drugs," commented Cynthia L. Sullivan, President and CEO.